Implantable system for glucose monitoring using fluorescence quenching

• US 7,704,704 B2
• Filed: 09/28/2006
• Issued: 04/27/2010
• Est. Priority Date: 09/28/2005
• Status: Expired due to Fees

• Current Assignee: Penn State Research Foundation, Texas A&M University System
• Original Assignee: Texas A&M University System
• Inventors: Pishko, Michael V., Rounds, Rebecca M., Yadavalli, Vamsi K., Ibey, Bennett L., Cote, Gerard L., Beier, Hope T.
• Primary Examiner(s): GITOMER, RALPH J
• Application Number:
  US11/529,280
• Publication Number:
  US 20070105176A1
• Time in Patent Office: 1,307 Days
• Field of Search: 435/14, 435/287.1, 435/288.7
• US Class Current: 435/14
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

This disclosure relates to systems, devices, and methods of sensing an analyte. An implantable sensor may be contacted with a test sample under conditions that permit a binding protein and a ligand of the sensor to interact in an analyte-dependent manner to produce an analyte-dependent signal, and (b) detecting the analyte-dependent signal with a detector. A binding protein may reversibly bind an analyte and/or a ligand. A binding protein may have a higher binding affinity for an analyte than for a ligand. A binding protein and a ligand may each include a fluorophore, the absorption and/or emission properties of which may change in an analyte-dependent manner. A binding protein and/or a ligand may be bound to an active or inactive substrate. Some embodiments of systems, devices, and methods may be practiced in vitro, in situ, and/or in vivo. Systems and/or devices of the disclosure may be configured to be wearable.

Claims

1. A system for measuring glucose, said system comprising:

(a) an implantable glucose-sensing device comprising;

a hydrogel having a matrix;

a functionalized polymer or functionalized nano-particle ligand;

a sugar-binding molecule comprising Concanavalin A, other sugar-binding lectins, glucose binding protein, glucose oxidase, or glucose apo-oxidase; and

a first fluorophore comprising a fluorescein, a rhodamine, a cyanine, or a fluorescent dye linked to the ligand or the sugar-binding molecule;

wherein the ligand and the sugar-binding molecule are present throughout the matrix of the hydrogel,

wherein the first fluorophore is a quenchable fluorophore having a fluorescent emission spectrum operable to be quenched upon binding or release of glucose by the sugar-binding molecule; and

(b) a light source configured and arranged to illuminate the implantable glucose sensing device with light of a wavelength sufficient to excite the quenchable fluorophore;

(c) a detector (a) in optical communication with the implantable glucose sensing device and (b) configured and arranged to detect at least at least one wavelength of light from the implantable glucose sensing device and produce a detected light signal;

(d) a processor in communication with the detector and configured and arranged to receive and process at least one detected light signal to produce a glucose metric;

(e) a display operably linked to the processor and configured and arranged to receive and display the glucose measurement; and

(f) a power source operably linked to at least the light source, the detector, the processor, and the display.

2. A system according to claim 1, wherein the glucose measurement is selected from the group consisting of a glucose concentration, a change in glucose concentration, a rate of change of glucose concentration, an amount of glucose, a change in an amount of glucose, a rate of change of the amount of glucose, and combinations thereof.

3. A system according to claim 1 further comprising an alarm in communication with the processor.

4. A system according to claim 3, wherein the alarm is configured and arranged to alert when the glucose measurement is below a preset threshold.

5. A system according to claim 3, wherein the alarm is configured and arranged to alert when the glucose measurement is above a preset threshold.

6. A system according to claim 3, wherein the alarm is configured and arranged to alert when the glucose measurement is within a preset range.

7. A system according to claim 1 further comprising a housing, wherein the light source, the detector, the processor, and the power source are at least partially enclosed within the housing.

8. A system according to claim 7, wherein the housing is configured and arranged to be worn by a subject.

9. A system according to claim 1, wherein the power source is a battery.

10. A system according to claim 1, wherein the light source is selected from the group consisting of a laser diode, a light-emitting diode, a light bulb, luciferase, and combinations thereof.

11. A system according to claim 1, wherein the detector is selected from the group consisting of a photodiode with an interference filter, a prism with a charge-coupled device array detection element, a grating with a charge-coupled device array detection element, a photomultiplier tube, and combinations thereof.

12. A system according to claim 1, wherein the ligand is immobilized on a substrate selected from the group consisting of an active substrate and an inactive substrate.

13. A system according to claim 1, wherein the sugar-binding molecule is immobilized on a substrate selected from the group consisting of an active substrate and an inactive substrate.

14. A system according to claim 1, wherein the functionalized polymer comprises a glycosylated dendrimer.

15. A system according to claim 14, wherein the glycosylated dendrimer comprises Polyamidoamine (PAMAM).

16. A system according to claim 14, wherein the glycosylated dendrimer comprises glycosyloxyethyl methacrylate (GEMA).

17. A system according to claim 1, wherein the functionalized nano-particle comprises a quantum dot, a metal particle, or a gold nanoshell with a silica core.

18. A system according to claim 1, wherein the functionalized nano-particle comprises glycosyloxyethyl methacrylate (GEMA).

19. A system according to claim 1, wherein the first fluorophore comprises carboxamido-(6-azidohexanyl).

20. A system according to claim 1, wherein the sugar-binding molecule has a binding affinity for glucose and a binding affinity for the ligand, and wherein the binding affinity for glucose is higher than the binding affinity for the ligand.

21. A system according to claim 1, wherein the sugar-binding molecule is operable to reversibly bind glucose.

22. A system according to claim 1, further comprising a second fluorophore comprising a fluoresceine, a rhodamine, a cyanine, or fluorescent dye linked to the sugar-binding molecule or ligand to which the first fluorescein is not linked.